2002 Fiscal Year Final Research Report Summary
Role of Histaminergic Neurons in Brain-GUT Interactions
| Project/Area Number |
11680778
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | Tohoku University |
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Principal Investigator |
FUKUDO Shin Tohoku University Graduate School of Medicine, Department of Behavioral Medicine, Professor, 大学院・医学系研究科, 教授 (80199249)
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| Project Period (FY) |
1999 – 2002
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| Keywords | brain-gut interactions / histamine / neurotransmitter / positron emission tomography / irritable bowel syndrome(IBS) / corticotropin-releasing hormone(CRH) / CRH-R1 / noradrenaline |
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| Research Abstract |
The aim of this study was to test the hypothesis that visceral stimulation induces neurotransmitter release, especially histamine, in the brain. The second hypothesis is that released histamine plays a role in modulating brain function. We expected that such analysis would result in identifying substance in brain-gut interactions. Microdilalysis experiment was performed using male Wistar rats. Colorectal distension of rats induced significant increase in histamine in the hippocampus from 1.34±0.47pmol/l to 4.68±0.58pmol/l (p<0.05). Anxiety-related behaviors were evoked when the rats were exposed to elevated plus maze after colorectal distention. Colorectal distention of rats also induced noradrenaline release in the hippocampus. These changes were blocked by administration of either non-specific corticotropin-releasing hormone (CRH) receptor antagonist α-helical CRH or specific CRH receptor-1 (CRH-R1) antagonist JTC017. In humans, positron emission tomography (PET) was performed for de
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tecting regional cerebral blood flow (rCBF) using H_2^<15>O which was synthesized with cyclotron. PET image under colonic distention was analyzed. Moreover, selective histamine H1 receptor antagonist d-chlorpheniramine was administered intravenously and PET image was analyzed. Colonic distention induced increase in rCBF in the thalamus, the anterior cingulate cortex, and the prefrontal cortex. Simultaneously, colonic distention inducedvisceral perception and emotion. These changes were significantly attenuated by administration and of d-chlorpheniramine. In patients with irritable bowel syndrome (IBS), left prefrontal cortex was activated. These results suggest that histamine noradrenaline, and CRH are released in the limbic system of the brain by colonic distention and that at least in part histamine H1 receptor and CRH-R1 are involved these phenomena. These results may open the door of possible therapeutic use of histamine H1 receptor antagonist or CRH-R1 antagonist for pathophysiological condition of brain-gut interactions. Less
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